Some SIV-infected rhesus monkeys have a rapidly progressive disease course, while others have a more prolonged course. A short course of disease is correlated with the in vivo evolution of macrophage tropic, syncytium forming viral variants. SIV-infected monkeys develop a variety of opportunist infections. Susceptibility or resistance to many diseases is linked to a particular Class I or Class II MHC type. The rhesus monkey colony at the TNO Medical Biological Laboratory (site of the Dutch Primate Center), Rijswijk, The Netherlands, is unique in that all of the animals are typed for Class I and II MHC alleles and their lineage is known for several generations. Some of these animals are used in SIV research. This provides a unique opportunity to study the association between progression of SIV infection and occurrence of opportunistic infections and MHC type in this model. All SIV-infected monkeys that have died have been examined histopathologically for the presence of syncytial cells and for opportunistic infections. The frequency of Class I and Class II MHC types in each group was compared statistically with the distribution of each type in the colony population. We found that a MHC class I serotype, Mamu-A26, was strongly associated with prolonged survival after SIV inoculation. Furthermore, CMV was strongly associated with Mamu-B6 (p<.001) and Mamu-B19 (p<.03). Candida was associated with Mamu-DR2 (p<.02), while Cryptosporidium was associated with DR3 (p<.001) and Mamu-A24 (p<.03). Pneumocystis was associated with Mamu-A26 (p<.03). Thus, the MHC type influences not only the rate of progression to SIV-induced AIDS, but also the types of opportunistic infections that may arise in an individual immunocompromised monkeys.